We are continuing our studies on pharmacological aspects of the mechanisms by which analgesic nephropathy is produced by chronic analagesic abuse, with particular attention on the possible role of acetaminophen. We have synthesized 15 metabolites of acetaminphen as analytical standards and have developed high performance liquid chromatographic procedures for their identification in urine. Trials have begun in mice to determine if ascorbic acid treatment modifies acetaminophen toxicity or the pattern of excreted metabolites. This is based on our prior observation that N-hydroxyacetaminophen reacts through a free-radicle mechanism. Collaborative studies are being developed to study these problems in the isolated perfused rate kidney.